Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility

Brett McKinnon, Samuel W. Lukowski, Sally Mortlock, Joanna Crawford, Sharat Atluri, Sugarniya Subramaniam, Rebecca L. Johnston, Konstantinos Nirgianakis, Keisuke Tanaka, Akwasi Amoako, Michael D Mueller, Grant W. Montgomery
Communications biology · 2022 · vol. 5(1) , pp. 600 · doi:10.1038/s42003-022-03541-3 · PMID:35725766 · PMC9209414 · W4283164841
article OA: gold CC0 ⤵ 20 in-corpus citations
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Endometrial mesenchymal stromal fibroblasts from women with endometriosis show incomplete differentiation and altered in vitro growth, suggesting a link to disease susceptibility.

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Abstract

Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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